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1.
Endocrinol. nutr. (Ed. impr.) ; 61(10): 523-530, dic. 2014. graf, tab
Article in English | IBECS | ID: ibc-130972

ABSTRACT

OBJECTIVE: To evaluate expression of somatostatin receptor subtypes 2 and 5 (SSTR 2 and 5) by RT/PCR and immunohistochemistry (IHC) in GH-secreting adenomas, seeking correlations with response to octreotide. METHODS: SSTR2 and 5 expression was tested by IHC (n = 37), RT/PCR (n = 36) or both (n = 13) in GH-secreting adenomas from 60 patients with acromegaly who had undergone pituitary surgery; 36 had been treated preoperatively with octreotide LAR for 3-6 months, and were categorized as responders (achievement of GH < 2.5 ng/mL and a normal age-adjusted IGF-1), partial responders (GH and IGF-1 reduction > 50% and > 30%, respectively) or non-responders. IHC was performed on a tissue microarray using specific antibodies directed to the carboxyl terminus of SSTR2 and 5. RESULTS: SSTR5 was the predominantly expressed receptor subtype by both IHC and RT/PCR in all tumors tested, regardless of whether they came from octreotide-naïve, octreotide-responsive, or octreotide-resistant patients. Immunostaining was concentrated in the cytoplasm. Neither SSTR2 nor SSTR5 expression correlated with baseline or post-octreotide GH or IGF-1 levels or tumor volume by either method. The agreement rate between RT/PCR and IHC was 77% in all 13 adenomas in which both methods were used. CONCLUSIÓN: Expression of these receptors does not guarantee an adequate response to somatostatin analogs; other functional aspects of this interaction, such as receptor homo- and heterodimerization, and the resulting signaling cascade, probably play a role in determining whether a patient will respond or not to these agents


OBJETIVOS: Evaluar la expresión de los receptores somatostatinérgicos 2 y 5 (SSTR 2 y 5) por RT/PCR e inmunohistoquímica (IHQ) en adenomas productores de GH, buscando correlaciones con la respuesta a octreótido. MÉTODOS: Se analizó la expresión de SSTR2 y SSTR5 mediante IHQ (n = 37), RT/PCR (n = 36) o ambas (n = 13) en adenomas productores de GH de 60 pacientes con acromegalia sometidos a cirugía; 36 habían recibido tratamiento preoperatorio con octreótido LAR durante 3-6 meses y fueron categorizados como respondedores (GH < 2.5 ng/mL e IGF-1 normal para edad), respondedores parciales (reducción de GH e IGF-1 a > 50% y > 30%, respectivamente) y no respondedores. La IHQ se realizó en una micromatriz de tejido, usando anticuerpos dirigidos contra el extremo carboxilo de SSTR 2 y 5. RESULTADOS: SSTR5 fue el receptor predominante en todos los tumores, tanto por IHQ como por RT/PCR, independientemente de si provenían de pacientes tratados (sensibles o resistentes) o no tratados con octreótido. La inmunotinción se localizó fundamentalmente en el citoplasma. No encontramos correlaciones entre la expresión de estos receptores por ninguno de los dos métodos con los niveles basales y post-octreótido de GH e IGF-1 ni con el volumen tumoral. La concordancia entre RT/PCR e IHQ fue del 77% en los 13 adenomas en los que ambos métodos fueron utilizados. CONCLUSIONES: La expresión de estos receptores no garantiza la respuesta farmacológica a análogos de la somatostatina; otros aspectos funcionales como la homo y heterodimerización, y la cascada de señalización producida, probablemente están involucrados en la determinación de la respuesta de cada paciente a estos agentes


Subject(s)
Humans , Acromegaly/drug therapy , Octreotide/pharmacokinetics , Receptors, Somatostatin/analysis , Growth Hormone-Secreting Pituitary Adenoma/drug therapy , Cytoplasm/ultrastructure , Somatostatin/therapeutic use , Immunohistochemistry/methods
2.
Endocrinol Nutr ; 61(10): 523-30, 2014 Dec.
Article in English, Spanish | MEDLINE | ID: mdl-25008035

ABSTRACT

OBJECTIVE: To evaluate expression of somatostatin receptor subtypes 2 and 5 (SSTR 2 and 5) by RT/PCR and immunohistochemistry (IHC) in GH-secreting adenomas, seeking correlations with response to octreotide. METHODS: SSTR2 and 5 expression was tested by IHC (n=37), RT/PCR (n=36) or both (n=13) in GH-secreting adenomas from 60 patients with acromegaly who had undergone pituitary surgery; 36 had been treated preoperatively with octreotide LAR for 3-6 months, and were categorized as responders (achievement of GH <2.5ng/mL and a normal age-adjusted IGF-1), partial responders (GH and IGF-1 reduction >50% and >30%, respectively) or non-responders. IHC was performed on a tissue microarray using specific antibodies directed to the carboxyl terminus of SSTR2 and 5. RESULTS: SSTR5 was the predominantly expressed receptor subtype by both IHC and RT/PCR in all tumors tested, regardless of whether they came from octreotide-naïve, octreotide-responsive, or octreotide-resistant patients. Immunostaining was concentrated in the cytoplasm. Neither SSTR2 nor SSTR5 expression correlated with baseline or post-octreotide GH or IGF-1 levels or tumor volume by either method. The agreement rate between RT/PCR and IHC was 77% in all 13 adenomas in which both methods were used. CONCLUSION: Expression of these receptors does not guarantee an adequate response to somatostatin analogs; other functional aspects of this interaction, such as receptor homo- and heterodimerization, and the resulting signaling cascade, probably play a role in determining whether a patient will respond or not to these agents.


Subject(s)
Adenoma/chemistry , Growth Hormone-Secreting Pituitary Adenoma/chemistry , Human Growth Hormone/metabolism , Neoplasm Proteins/biosynthesis , Octreotide/therapeutic use , Receptors, Somatostatin/biosynthesis , Acromegaly/etiology , Adenoma/complications , Adenoma/drug therapy , Adenoma/surgery , Antineoplastic Agents, Hormonal/therapeutic use , Combined Modality Therapy , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Growth Hormone-Secreting Pituitary Adenoma/complications , Growth Hormone-Secreting Pituitary Adenoma/drug therapy , Growth Hormone-Secreting Pituitary Adenoma/surgery , Human Growth Hormone/analysis , Humans , Hypophysectomy , Insulin-Like Growth Factor I/analysis , Neoplasm Proteins/genetics , Real-Time Polymerase Chain Reaction , Receptors, Somatostatin/genetics , Tissue Array Analysis
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